Metformin suppressed tendon injury-induced adhesion via hydrogel-nanoparticle sustained-release system.
Int J Pharm
; 642: 123190, 2023 Jul 25.
Article
em En
| MEDLINE
| ID: mdl-37391109
ABSTRACT
Tendon adhesion is one of the sequelae of tendon injury and can lead to disability in severe cases. Metformin is a commonly used antidiabetic drug. Some studies had shown that metformin could reduce tendon adhesion as well. Considering the characteristic of low absorption rate and short half-life, we established a sustained-release system, i.e., hydrogel-nanoparticle system to deliver metformin. In vitro, metformin could effectively suppress TGF-ß1-induced cell proliferation and accelerate cell apoptosis, according to cell counting kit-8, flow cytometry, and 5-ethynyl-2'-deoxyuridine (EdU) staining studies. In vivo, hydrogel-nanoparticle/metformin system could significantly lower adhesion scores and improve the gliding function of repaired flexor tendons, as well as decrease the expression of fibrotic proteins Col1a1, Col3a1, and α-smooth muscle actin (α-SMA). Histological staining revealed that the inflammation had subsided and that the gap between the tendon and the surrounding tissue was wider in the hydrogel-nanoparticle/metformin treatment group. Finally, we speculated that effect of metformin on reducing tendon adhesion might be achieved by regulating both Smad and MAPK-TGF-ß1 signaling pathways. In conclusion, metformin delivered through hydrogel-nanoparticle sustained-release system may be a promising strategy for coping with tendon adhesion.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Traumatismos dos Tendões
/
Nanopartículas
/
Metformina
Limite:
Humans
Idioma:
En
Revista:
Int J Pharm
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
China